睡眠障碍患者血浆代谢标志物研究

Plasma metabolic markers in patients with insomnia disorder

目的筛选睡眠障碍患者血液中的代谢标志物,并分析其异常代谢通路。方法选取2021年1—12月上海健康医学院附属嘉定区中心医院睡眠障碍患者30例(睡眠障碍组)、健康体检者30名(正常对照组)。收集所有研究对象的一般资料。采用超高效液相色谱串联质谱(UPLC-MS/MS)检测所有研究对象的血浆代谢物。依据VIP值、差异倍数(FC)和P值筛选出睡眠障碍组与正常对照组之间有显著意义的差异代谢物。对差异代谢物进行京都基因与基因组百科全书(KEGG)通路富集分析。结果共检出1656个代谢物,筛选出睡眠障碍组与正常对照组之间有显著意义的差异代谢物181个。正离子模式筛选出115个(表达上调61个、表达下调54个),VIP值居前10位的代谢物分别为乙二胺四乙酸、肉碱、N-(1-氨基-3,3-二甲基-1-氧代丁-2-基)-1-戊基-1h-吲哚-3-甲酰胺、[1-(环己基甲基)-1h-吲哚-3-羰基]-l-缬氨酸甲酯、二丁卡因、甘油磷酸胆碱、次黄嘌呤、棕榈酰血清素、去铁胺d2、亚麻酰肉碱。负离子模式筛选出66个(表达上调38个、表达下调28个),VIP值居前10位的代谢物分别为柠檬酸盐、牛磺酸、鼠李素、尿酸、丙酮酸盐、尿囊素、3',5'-环肌苷-磷酸、D-乳酸、(+)-6-氨基青霉烷酸、油酸。KEGG通路富集分析结果显示,差异代谢物涉及的通路为癌症的中枢碳代谢、腺苷三磷酸结合盒转运蛋白和蛋白质消化吸收等。结论筛选出睡眠障碍患者具有代表性的代谢物和代谢通路,可为睡眠障碍的诊断和治疗提供潜在的靶点。

Objective To screen metabolic markers in the blood of patients with insomnia disorder,and to analyze the abnormal metabolic pathways.Methods Totally,30 patients with insomnia disorder(insomnia disorder group)and 30 healthy subjects(healthy control group)from January to December 2021 at Jiading District Central Hospital of Shanghai University of Medicine and Health Sciences were enrolled.The general data were collected.Ultra performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS)was used to determine plasma metabolites.Based on VIP value,fold change(FC)and P value,significantly differential metabolites were screened between insomnia disorder group and healthy control group.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment pathway analysis was performed on differential metabolites.Results Totally,1656 metabolites were determined,and 181 differential metabolites between insomnia disorder group and healthy control group were selected.Among them,115 metabolites were screened for positive ion mode(61 cases of up-regulation and 54 cases of down-regulation),and the top 10 metabolites with VIP values were ethylenediaminetetraacetic acid,carnitine,N-(1-amino-3,3-dimethyl 1-oxobutan-2-yl)-1-pentyl-1h-indole-3-formamide,[1-(cyclohexylmethyl)-1h-indole-3-carbonyl]-l-valine methyl ester,di tetracaine,glycerophosphate choline,hypoxanthine,palmitoyl serotonin,deferoxamine d2 and linolenic carnitine.The 66 metabolites(38 cases of up-regulation and 28 cases of down-regulation)were screened for negative ion mode,and the top 10 metabolites with VIP values were citrate,taurine,rhamnocitrin,uric acid,pyruvate,allantoin,3',5'-cyclic inosine monophosphate,D-lactic acid,(+)-6-aminopenicillanic acid and oleic acid.The enrichment analysis of KEGG pathway showed that the differential metabolites were involved in the central carbon metabolism of cancer,ATP-binding cassette transporter and protein digestion and absorption.Conclusions Screening out representative metabolites and metabolic pathways in patients with insomnia disorder can provide potential targets for the diagnosis and treatment of insomnia disorder.